Several lines of evidence have pointed to a role for microbes found in the gastrointestinal tract in the evolution of Alzheimer’s disease (AD) pathogenesis.¹ Other studies have shown that the gut microbes of people with symptomatic AD differ from the microbiomes of healthy people of the same age.² Taking this research one step further, new findings by Ferreiro et al published in Science Translational Medicine suggest that even the gut microbiome of patients with early, pre-symptomatic AD have an altered taxonomic composition compared with that of healthy individuals, despite having similar diets.³

During this early stage of AD, which can last two decades or more, affected patients accumulate the proteins amyloid beta and tau in their brains but may only suffer from mild memory loss, with no functional impairment in daily activities.^3,4 Early detection of AD pathology opens the door for the design of preventive treatments.

The 2023 cross-sectional observational study involved 164 cognitively normal older patients (n=68-94) who were tested for the presence of the AD proteins ?-amyloid (A?) and tau pathological biomarkers in their brains.³ Cognitive tests were also used to identify patients with preclinical AD. Of the 164 participants, about a third, or 49 patients, had signs of early AD. Using fecal samples, the scientists then compared the bacteria found in the guts of the 49 preclinical cases to patients who did not have signs of AD proteins to detect differences in their microbiome.³

An analysis revealed that healthy people and people with preclinical Alzheimer’s disease have distinctly different gut bacteria—both in terms of the species of bacteria present and the biological processes they are involved in—despite consuming the same diet.³ To account for the impact of diet on the composition of the gastrointestinal microbiome, the researchers assessed patient nutritional profiles from stool-matched 24-hour diet logs and found no significant difference between the healthy and preclinical AD groups in the overall caloric intake, caloric source distribution, or intake of any major nutrient group or specific vitamins or minerals.³

The differences in gut microbiome profiles correlated with amyloid and tau levels in preclinical AD, which rise before cognitive symptoms appear, but did not correlate with the onset of neurodegeneration.³ Specific gut microbe species most associated with preclinical AD status included Dorea formicigenerans (P < 0.001; all P values from regression analyses are Benjamini-Hochberg adjusted), Oscillibacter sp. 57_20 (P < 0.001), Faecalibacterium prausnitzii (P < 0.001), Coprococcus catus (P < 0.001), and Anaerostipes hadrus (P < 0.001). Furthermore, patients in the preclinical stages of AD had higher populations of bacteria involved in breaking down arginine and ornithine—two amino acids that are involved in protein buildup—while patients without preclinical AD had more bacteria involved in glutamate degradation, which may protect neurons.³

These findings may help clinicians begin identifying individuals at a higher risk of developing dementia and may advance the research on microbiome-based treatments to prevent cognitive decline. Researchers are just beginning to understand the gut microbiome’s effect on neurodegeneration. For more information about Alzheimer’s disease and cognitive decline, please visit the following resources:

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References

1. Varesi A, Pierella E, Romeo M, et al. The potential role of gut microbiota in Alzheimer’s disease: from diagnosis to treatment. Nutrients. 2022;14(3):668. doi:3390/nu14030668
2. Vogt NM, Kerby RL, Dill-McFarland KA, et al. Gut microbiome alterations in Alzheimer’s disease. Sci Rep. 2017;7(1):13537. doi:1038/s41598-017-13601-y
3. Ferreiro AL, Choi J, Ryou J, et al. Gut microbiome composition may be an indicator of preclinical Alzheimer’s disease. Sci Transl Med. 2023;15(700):eabo2984. doi:1126/scitranslmed.abo2984
4. Breijyeh Z, Karaman R. Comprehensive review on Alzheimer’s disease: causes and treatment. Molecules. 2020;25(24):5789. doi:3390/molecules25245789